By: Kerri Fitzgerald
A phase 1b/2 study added the investigational BCL-2 inhibitor lisaftoclax to pomalidomide/dexamethasone (Pd) and daratumumab/lenalidomide/dexamethasone (DRd) regimens and observed improved outcomes in patients with relapsed or refractory multiple myeloma (MM) and AL amyloidosis.
The study was presented by Jack Khouri, MD, of the Cleveland Clinic, as part of the SOHO 2025 Annual Meeting.
The multicenter study included 52 patients (42 with MM, 10 with AL amyloidosis; median age, 69.5 years) who received these combination therapies. Most patients were men (53.5%), and patients had received a median of three prior lines of therapy.
Among 49 patients in the safety cohort, 34 (69.4%) experienced any-grade lisaftoclax treatment-related adverse events, including neutropenia (20.4%), thrombocytopenia (6.1%), leukopenia (10.2%), nausea (16.3%), abdominal distension (10.2%), diarrhea (12.2%), and constipation (8.2%).
Grade ≥3 adverse events occurred in 11 patients, including neutropenia (14.3%) and febrile neutropenia (2.0%). No drug-drug interactions were reported.
In a cohort of 31 evaluable patients, 19 responded to treatment, including nine partial responses (PRs), seven very good partial responses (VGPRs), and three complete responses (CRs). The overall response rate (ORR) was 61.3%.
In another cohort of four evaluable patients, two achieved CR and two achieved VGPR or better. In a third cohort of seven patients, one achieved CR, four achieved VGPR, one achieved PR, and five achieved VGPR or better. The ORR was 85.7%.
The study was supported by Ascentage Pharma Group Corp Ltd.
Reference
Ailawadhi S, Chanan-Khan A , Khouri J, et al. Lisaftoclax (APG-2575) combined with novel therapeutic regimens in patients with relapsed or refractory (R/R) multiple myeloma (MM) or immunoglobulin light-chain (AL) amyloidosis. Abstract #MM-718. Presented at the Society of Hematologic Oncology 2025 Annual Meeting; September 3-6, 2025; Houston, Texas.
Visit the SOHO 2025 meeting news page for more coverage from the meeting.
